1. Field of the Invention
This invention relates to a novel alkaloid compound which is useful as a chemotherapeutic agent for the remission of leukemia in animals.
2. Description of the Prior Art
The search for chemical compounds which are chemotherapeutically active against leukemia systems has revealed a series of cephalotaxine esters which are naturally occurring in the plant material of the Japanese plum yew, Cephalotaxus harringtonia. [Powell et al., Tetrahedron Lett. 4081(1969); Powell et al., Tetrahedron Lett. 815 (1970); Mikolajczak et al., Tetrahedron 28: 1995 (1972); Powell et al., J. Pharm. Sci. 61(8): 1227-1230 (August 1972); U.S. Pat. No. 3,793,454; and U.S. Pat. No. 3,870,727.] Two of the esters, harringtonine and homoharringtonine have been approved for preclinical evaluation at the National Cancer Institute. In addition, several synthetic esters of cephalotaxine possessing antileukemic activity have been prepared [Mikolajczak et al., J. Med. Chem. 20: 328-332 (1977)].
Another antileukemic and antitumor agent, taxol, has been isolated from the stem bark of the western yew, Taxus brevifolia [Wani et al., J. Amer. Chem. Soc., 93: 2325-2327 (1971)]. This was the first compound possessing the texane ring which has been shown to have any chemotherapeutic activity. Taxol is characterized by the following chemical structure: ##STR2## wherein R.sup.1 =OH
R.sup.2 =H ##STR3## R.sup.4 =OAc PA1 baccatin III, wherein PA1 10-desacetyl baccatin III, wherein PA1 baccatin V, wherein PA1 10-desacetyl baccatin V, wherein
It is similar in structure to a series of related but inactive compounds, including:
R.sup.1 =OH, R.sup.2 =H, R.sup.3 =OH, R.sup.4 =OAc; PA2 R.sup.1 =OH, R.sup.2 =H, R.sup.3 =OH, R.sup.4 =OH; PA2 R.sup.1 =H, R.sup.2 =OH, R.sup.3 =OH, R.sup.4 =OAc; and PA2 R.sup.1 =H, R.sup.2 =OH, R.sup.3 =OH, R.sup.4 =OH.